Siah-1 is associated with expression of hypoxia-inducible factor-1α in oral squamous cell carcinoma

Auris Nasus Larynx. 2017 Apr;44(2):213-219. doi: 10.1016/j.anl.2016.06.007. Epub 2016 Sep 8.

Abstract

Objective: Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of the HIF-1α and HIF-1β subunits. HIF-1 is a central regulator of responses to hypoxia; it enhances metastasis-related factors such as matrix metalloproteinases and vascular endothelial growth factor (VEGF). We have reported critical roles for HIF-1α in tumor microenvironments, and oncogenic properties of HIF-1α have been suggested in malignancies. Seven in absentia homologue (Siah) appeared to upregulate HIF-1 production, which prompted us to investigate the Siah association with HIF-1α expression in oral squamous cell carcinoma (OSCC).

Methods: Samples from fifty-five patients with OSCC were evaluated by immunohistochemistry for the protein expressions of Siah-1 and -2, HIF-1α, and VEGF. The expression levels of each protein and clinicopathological data were statistically analyzed.

Results: Siah-1 and, Siah-2, HIF-1α, and VEGF were immunolocalized on the cell membranes and cytoplasm of the tumor cells. The expression of Siah-1 showed a linear dependence on the expression of HIF-1α (r=0.627, p<0.001). In 17 cases of the large tumor size category (T3 and 4), the mean Siah-1 expression score was significantly higher than in 41 cases of the small tumor size category (T1 and 2; p=0.001). In addition, in 16 cases of the lymph node metastasis-positive category (N1-3), the mean Siah-1 expression score was significantly higher than that in 42 cases of the lymph node metastasis-negative category (N0, p=0.001).

Conclusion: These results suggested that the expressions of Siah-1 and HIF-1α were clearly correlated in OSCC. Moreover, Siah-1 appears to be correlated with clinicopathological data, particularly tumor size.

Keywords: HIF-1α; Oral squamous cell carcinoma; Siah-1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism*
  • Female
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mouth Neoplasms / metabolism*
  • Nuclear Proteins / metabolism*
  • Squamous Cell Carcinoma of Head and Neck
  • Ubiquitin-Protein Ligases / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins